A systematic review investigated the adverse events of cannabis-based medicines in 23 randomised controlled trials.36 The cannabis-based preparations examined were nabiximols, oral whole-plant extracts and isolated delta-9-tetrahydrocannabinol (THC). The rate of non-serious adverse events was higher among participants assigned to the cannabis-based medicine groups than to the control, but not for serious adverse events. The most commonly reported adverse event in the active groups was dizziness (15.5%).

Patients who intake cannabis-based medicines over the long term may develop tolerance, not only for the psychoactive but also for the cardiovascular side-effects. Long-term intake of cannabis-based medicines should therefore not be stopped abruptly.1 The overall risk for physical and psychic dependency seems to be low in comparison with opioids, tobacco, alcohol and benzodiazepines.1

Cannabinoids can change DNA synthesis and cell reproduction in vitro, but there is no evidence of mutagenic effects or of long-term carcinogenicity of orally administered cannabinoids.37

Interactions

Pharmacokinetic interactions from medical cannabis and cannabinoids may occur because of interference with metabolism at the cytochrome P450 subsystem in the liver (Cyt P450 3A4), and may theoretically lead to delayed elimination of, for example, fentanyl. Interactions are also possible with known inhibitors (ritanovir, estradiol etc.) or inductors of Cyt P450 3A4 (rifampicin, phenytoin, carbamazepin, St John’s wort).11

There is evidence that cannabinoids interact pharmacodynamically with levodopa and similar anti-Parkinson drugs.38 Currently, the use of anti-Parkinson drugs is a contraindication for cannabis-based medicines.

Little is known so far about possible interactions with other centrally active drugs, especially psychiatric medication or with herbal products.

Contraindications

Epidemiologic data have shown an association between heavy adolescent use of smoked cannabis with the development of psychotic disorders.39 Even though no causality between use of cannabis and psychotic disorders has been shown, a history or family history of psychotic disorders is generally seen as contraindication for the use of cannabis-based medicines.

The placental barrier is crossed by THC, and also accumulates in breast milk. Controversy exists regarding findings for the effects of cannabinoids on male reproduction, although there is some evidence that cannabinoids decreases sperm count and motility.40 Therefore, pregnant and breast-feeding women, and women and men who wish to have children, must not use cannabinoid products.

Some medical cannabis or cannabinoid preparations contain additives, e.g. sesame oil, which are contraindicated in people who may be allergic to these substances.41

Warnings/precautions

The use of cannabis-based medicines might impair the ability to drive a car, especially during any phases during which a dosage is being increased.

Legal notice
The present documentation has been compiled by the CAM-CANCER Project with all due care and expert knowledge. However, the CAM-CANCER Project provides no assurance, guarantee or promise with regard to the correctness, accuracy, up-to-date status or completeness of the information it contains. This information is designed for health professionals. Readers are strongly advised to discuss the information with their physician. Accordingly, the CAM-CANCER Project shall not be liable for damage or loss caused because anyone relies on the information.